CAS E REP O R T Open Access Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report Francisco Rivera 1* , Sara Anaya 1 , Javier Pérez-Álvarez 2 , Maria D Sánchez de la Nieta 1 , María C Vozmediano 1 , Julia Blanco 2 Abstract Introduction: Henoch-Schönlein purpura is a systemic disease with frequent renal involvement, characterized by IgA mesangial deposits. Streptococcal infection can induce an abnormal IgA immune response like Henoch- Schönlein purpura, quite similar to typical acute post-infectiou s glomerulonephritis. Indeed, hypocomplementemia that is typical of acute glomerulonephritis has also been described in Henoch-Schönlein purpura. Case presentation: We describe a 14-year-old Caucasian Spanish girl who developed urinary abnormalities and cutaneous purpura after streptococcal infection. Renal biopsy showed typical findings from Henoch-Schönlein purpura nephritis. In addition, she had low serum levels of complement (C4 fraction) that persiste d during follow- up, in spite of her clinical evolution. She responded to treatment with enalapril and steroids. Conclusion: The case described has, at least, three points of interest in Henoch-Schönlein purpura: 1) Initial presentation was preceded by streptococcal infection; 2) There was a persistence of low serum levels of complement; and 3) There was response to steroids and angiotensin-converting enzyme inhibitor in the presence of nephrotic syndrome. There are not many cases described in the literature with these characteristics. We conclude that Henoch-Schönlein purpura could appear after streptococcal infection in patients with abnormal complement levels, and that steroids and angiotensin-converting enzyme inhibitor could be successful treatment for the disease. Introduction Henoch-Schönlein purpura (HSP) is a systemic disease with frequent renal involvement, characterized by IgA mesangial deposits. Its etiology is unknown, but several infections have been described as trigger agents [1]. Streptococcal infection could induce an abnormal IgA immune responses like HSP, quite similar to typical acute post-infectious glomerulonephritis (AGN) [2,3]. Indeed, hypocomplemetemia that is typical of AGN has been also described in HSP [4]. We describe a young girl patient who developed urin- ary abnormalities and cutaneous purpura after strepto- coccal infection. Renal biopsy showed findings typical o f HSP nephritis, with prominent mesangial IgA deposits. In addition, she had low serum levels of C4 that persist during follow-up , in spite of her clinical evolution. We conclude that HSP can appear after streptococcal infec- tion in patients with abnormal complement levels. Case presentation A 14-year-old Caucasian Spanish girl without previous diseases or known renal diseases, had an upper respira- tory tract infection i n December 2007 with malaise, no cough, tonsilar swelling, sore throat and fever >38°C, which were treated with codeine and acetaminophen. Four weeks la ter, she developed arthralgias and asthenia followed by purpura on legs, arms and abdomen. There was no abdominal pain or oedema. During physical examin ation, blood pressure was 100/45 mmHg and she did not have oedemas; she presented palpable purpura. Urine analysis revealed microscopic haematuria, protei- nuria (ratio protein/creatinine 3.4 mg/mg) and granular * Correspondence: friverahdez@telefonica.net 1 Sección de Nefrología. Hospital General de Ciudad Real. c/Tomelloso s/n, 13005 Ciudad Real. Spain Rivera et al. Journal of Medical Case Reports 2010, 4:50 http://www.jmedicalcasereports.com/content/4/1/50 JOURNAL OF MEDICAL CASE REPORTS © 2010 Rivera et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited. casts with normal renal function (serum creatinine 0.8 mg/dl). Some other laboratory finding s were: haemoglo- bin 12.7 g/dl, white cell count 6300 μ,plateletcount 226000 μl, antistreptolisin-O 465 U/ml (normal under 240), serum total proteins 6 g/dL and albumin 3.7 g/dL. Coagulation study was not altered. ANA, anti-DNA, ANCAS, antibodies anti-MBG, crioglobulins, lupus anticogalulant and anticardi olipin antibodies were nega- tives. IgG 969 mg/dl, IgA 150 mg/dl, IgM 93 mg/dl. C3 87 mg/dl and C4 low (13 mg/dl, normal interval 15-45). Abdominal ultrasound revealed normal kidneys. We performed biopsies of the purpuric lesions and the kid- ney. In the former, there was leukocytoclastic vasculitis. Upon renal biopsy, we examined 42 glomeruli with dif- fuse proliferative endocapillary proliferation with a cer- tain degree of mesangial proliferation and increased mesangial matrix, without humps, leukocyte infiltration or crescents. Moreover, there was no vasculitis. Direct immuno fluorescence revealed the deposition of granular IgA and with less intensity C3 and fibrinogen in the mesangium. The lesions were graded according to ISKD and were classified as stages II (Figure 1). Ultrastructural study with electronic microscopy was not done. Treatment was initiated with oral prednisone 1 mg/Kg/day. Nevertheless, the illness of our patient evolved to overt nephrotic syndrome (h ypoalbuminemia, oedemas) and enalapril (5 mg/day) plus aspirin (100 mg/day) were added as treatment. Prednisone was main- tained for 16 weeks with progressive dose tapering. Sub- sequently, we observed the progressive decrease of proteinuria that remitted completely (Figure 2). In the last revision, performed nine months after initial presen- tation, our patient only had microhaematuria as unique manifestation of renal disease. Serum ASLO indeed decreased by mor e than 50% compared to initial values. Curiously, our patient maintained low levels of serum C4 without modification of serum C3 levels. See the evolution at Figure 3. Discussion The case described has, at least, three points of interest in HSP: 1) Initial pres entation was preceded by strepto- coccal infection; 2) There was persistence of low serum levels of C4; a nd 3) There was response to steroids and angiotensin converting enzyme inhibitor (ACEI) in the presence of nephrotic syndrome. We are going to dis- cuss these points in the following paragraphs. Both AGN and H SP nephritis could appear after anti- gen exposure with similar clinical presentation such hematuria, edemas and hypertension [2,5,6]. In this case, streptococcus infection was supported by clinical data and high serum ASLO levels that decreased subse- quently. Moreover, the c linical picture an d the absence of diabetes or other debilitating diseases indicates that thepresenceofstaphyloccocus infection-associated glo- merulonephritis mimicking IgA nephropathy seems unlikely [7]. On the one hand, the presence of hypo- complementemia would make AGN to be a m ore likely diagnosis. Although in this GN the complement syst em is usually activated by alternative pathway, it has been described as the activation by classical pathway, charac- terized by low levels of C4 without decrease of C3, as we observed in our patient. Moreover, GNA has also been described as having the presence of systemic vas- culitis affecting skin, bowel and oth er organs mimicking HSP [5,6]. On the other hand, the presence of purpura and absence of typical nephritic syndrome supported the diagnosis of HSP. Indeed, it has been also described that ASLO titer positivity is associated with a significant increase in the risk of HSP and renal involvement is more common among cases with positive elevated titers [8]. Finally, renal biopsy was essential to establish defini- tive diagnosis, as occured in many glomerular diseases. The presence of mesangial proliferation without leuko- cyt e infiltration and the presence of IgA deposits led us to a definitive diagnosis of HSP. These findings remark the importance of renal biopsy in the diagnosis of the majority of glomerular diseases because clinical manifes- tations ma y be similar in many different glomerular dis- eases [9]. We think that our patient did not have superimposed minimal change disease, although it is impossible to ensure since we did not do an electronic microscopy study. However, if the biopsy of our patient had podocyte fusion, it would explain by nephrotic pro- teinuria as an unspecific finding. Although there are no serum markers of HSP, the increase of serum IgA in more than 50% of patients without modification of complement serum levels has been found [10]. However, in some patients with HSP nephrit is transient hypocomplemetemia may appear [4]. Indeed, congenital defects of complement fractions are recognized predisposing factors in the development of other systemic diseases such as lupus erythematosus, Sjögren and connective tissue diseases. Furthermore, several authors have described in HSP the presence of low C4 serum levels in acute phase of nephritis in 17%, and about 20% in chronic evolution. This hypocomple- metemia is not related to the severity of the disease in most of patients [4]. In our case, the low C4 levels did not have any rela- tion with the severity of renal evolution. Whether the hypocomplementemia is the result of complement acti- vation after immunological activation from immune complex or indicates a congenital defect is difficult to clarify. In our case, the presence of low serum leve ls of C4, irrespective of clinical evolution, allows us to con- sider a congenital deficit because when nephropathy Rivera et al. Journal of Medical Case Reports 2010, 4:50 http://www.jmedicalcasereports.com/content/4/1/50 Page 2 of 5 Figure 1 Photomicrographs of kidney biopsy specimens. (A and B) Endocapillary diffuse proliferation with irregular distribution among glomerular segments. (C) Mesangial deposits of IgA with some parietal deposits and (D) deposits of C3 in mesangial areas. Figure 2 Analytical evolution. Rivera et al. Journal of Medical Case Reports 2010, 4:50 http://www.jmedicalcasereports.com/content/4/1/50 Page 3 of 5 reached complete remission, the levels of serum C4 remained low. Recently, it has been described that C4 null alleles were significantly more common among HSP patients than in controls and so children with C4 deficiencies mayhaveincreasedriskofdevelopingHSP[11]. Furthermore, the C4 congenital deficit is the most fre- quent complement congenital deficit, which in many occasions has no clinical consequences. However, in patients with other immunological alterations such abnormal IgA 1 O-glycosilation [12], the infection with streptococcal antigens -or other antigenic stimuli- could trigger the development of HSP nephritis, as we observed in our case. On the other hand, the so called “ Nephritis-Asso- ciated-Plasmin-Receptor” (NAPlr) which has been found in the glomeruli and in sera of many patients with AGN [13,14] has been also found in renal glomeruli in 10/33 of pat ients with PSH and it is likely that the d eposition of NAPlr in the mesangium may have a role in the pathogenesis of HSP [15]; and this antigen may be related to the pathogenesis in some patients with SHP [16]. It is attractive to speculate about streptococcal infection being involved in both GN, with the participation of NAPlr antigen. In our case, we can speculate that streptococcal infection in a patient with abnormal IgA response and congenital complement abnormalities derives from the development of HSP nephritis. The treatment of HSP is controversial and the use of steroids and immunosuppressive drugs must be reserved for cases with a severe form of presentation. Corticos- tero ids produce consistent benefits and reduce the odds of developing persistent renal disease [17]. In our case, the development of nephrotic syndrome allows us to start treatment with steroids and the evolution wa s quite good. In our patient, we added a low dose of ena- lapril as an antiproteinuric measure, despite our patient having a completely normal blood pressure because of the well demonstrated b eneficial effect of ACEI in idio- pathic IgA nephropathy [18]. Therefore, the use of ACEI would certainly influence its evolution. Conclusion We conclude that HSP could appear after streptococcal infection in patients with abnormal complement levels and irreversible glomerular injury could be prevented if treatment with steroids were initiated early. Figure 3 Evolution of serum levels of complement. Rivera et al. Journal of Medical Case Reports 2010, 4:50 http://www.jmedicalcasereports.com/content/4/1/50 Page 4 of 5 Consent Written informed consent was obtained from the par- ents of our patient for publication of this case report and accompanying images. A copy of t he written con- sent is available for review by the Editor-in-Chief of this journal. Acknowledgements Prof Bernardo Rodriguez-Iturbe has made substantial contributions to the elaboration of the manuscript and his advice has improved our understanding of many aspects of the case described. This Case Report has been discussed in the 15 th Meeting of Spanish Nephropathology Club, held in Madrid, 2008. Author details 1 Sección de Nefrología. Hospital General de Ciudad Real. c/Tomelloso s/n, 13005 Ciudad Real. Spain. 2 Servicio de Anatomía Patológica. Hospital Clínico Universitario San Carlos. Av. Prof. Martin Lagos, s/n. 28040 Madrid. Spain. Authors’ contributions F Rivera, S Anaya, MD Sánchez de la Nieta and MC Vozmediano analyzed and interpreted our patient data regarding the renal disease. J Pérez-Alvárez and J Blanco performed the histological examination of the kidney, and were major contributors in writing the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 31 December 2008 Accepted: 11 Februar y 2010 Published: 11 February 2010 References 1. Dedeoglu F, Kim S, Sundel R: Clinical manifestations and diagnosis of Henoch-Schönlein purpura. Waltham MA: UpToDateBasow DS 2008. 2. Al-Ruqeishi N, Venugopalan P, El Nour I, Date A: IgA nephropathy presenting clinical features of poststreptococcal glomerulonephritis. Pediatr Nephrol 2003, 18:956-958. 3. Rodriguez-Iturbe B, Musser JM: The Current State of Poststreptococcal Glomerulonephritis. JASN 2008, 19:1855-1864. 4. Motoyama O, Iitaka K: Henoch-Schönlein purpura with hypocomplementemia in children. Pediatr Int 2005, 47:39-42. 5. Goodyer PR, de Chadarevian JP, Kaplan BS: Acute poststrepotococcal glomerulonephritis mimicking Henoch-Schönlein purpura. J Pediatr 1978, 93:412-415. 6. Matsukura H, Ohtsuki A, Fuchizawa T, Miyawaki T: Acute poststreptococcal glomerulonephritis mimicking Henoch-Schönlein purpura. Clin Nephrol 2003, 59:64-65. 7. Satoskar AA, Nadasdy G, Plaza JA, Sedmak D, Shidham G, Hebert L, Nadasdy T: Staphylococcus infection-associated glomerulonephritis mimicking IgA nephropathy. Clin J Am Soc Nephrol 2006, 1:1179-1186. 8. Al-Sheyyab M, Batieha A, El-Shanti H, Daoud A: Henoch-Schönlein purpura and streptococcal infection: a prospective case-control study. Ann Trop Paediatr 1999, 19:253-255. 9. Rivera F, López-Gómez JM, Pérez García R: Clinicopathological correlations of renal pathology in Spain. Kidney Int 2004, 66:898-904. 10. Smith GC, Davidson JE, Hughes DA, Holme E, Beattie TJ: Complement activation in Henoch-Schönlein purpura. Pediatr Nephrol 1997, 11:477-480. 11. Stefansson Thors V, Kolka R, Sigurdardottir SL, Edvardsson VO, Arason G, Haraldsson A: Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura. Scand J Immunol 2005, 61:274-278. 12. Allen AC, Willis FR, Beattie TJ, Feehally J: Abnormal IgA glycosylation in Henoch-Schönlein purpura restricted to patients with clinical nephritis. Nephrol Dial Transplant 1998, 13:930-934. 13. Yamakami K, Yoshizawa N, Wakabayashi K, Takeuchi A, Tadakuma T, Boyle MDP: The potencial Role for Nephritis-Associated Plasmin Receptor in Acute poststreptococcal Glomerolonephritis. Methods 2000, 21:185-197. 14. Yoshizawa N, Yamakami K, Fujino M, Oda T, Tamura K, Tsumoto K, Sugisaki T, Boyle MDP: Nephritis-Associated Plasmin Receptor and Acute Poststreptococcal Glomerulonephritis: Characterization of the Antigen and Associated Immune Response. J Am Soc Nephrol 2004, 15:1785-1793. 15. Masuda M, Nakanishi K, Yoshizawa N, Iijima K, Yoshikawa N: Group A Streptococcal Antigen in the Glomeruli of Children with Henoch- Schönlein Nephritis. Am J Kidney Dis 2003, 41:366-370. 16. Kikuchi Y, Yoshizawa N, Oda T, Imakiire T, Suzuki S, Miura S: Streptococcal origin of a case of Henoch-Schoenlein purpura nephritis. Clin Nephrol 2006, 65:124-128. 17. Weiss PF, Feinstein JA, Luan X, Burnham JM, Feudtner C: Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review. Pediatrics 2007, 120:1079-1087. 18. Praga M, Gutierrez E, Gonzalez E, Morales E, Hernandez E: Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 2003, 14:1578-1583. doi:10.1186/1752-1947-4-50 Cite this article as: Rivera et al.: Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report. Journal of Medical Case Reports 2010 4:50. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Rivera et al. Journal of Medical Case Reports 2010, 4:50 http://www.jmedicalcasereports.com/content/4/1/50 Page 5 of 5 . nephritis. Nephrol Dial Transplant 1998, 13:930-934. 13. Yamakami K, Yoshizawa N, Wakabayashi K, Takeuchi A, Tadakuma T, Boyle MDP: The potencial Role for Nephritis- Associated Plasmin Receptor in Acute poststreptococcal. CAS E REP O R T Open Access Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report Francisco Rivera 1* , Sara Anaya 1 , Javier. San Carlos. Av. Prof. Martin Lagos, s/n. 28040 Madrid. Spain. Authors’ contributions F Rivera, S Anaya, MD Sánchez de la Nieta and MC Vozmediano analyzed and interpreted our patient data regarding